Cyclic DGR-peptidomimetic containing a bicyclic reverse turn inducer as a selective alpha(v)beta (5) integrin ligand.

3-Aza-6,8-dioxabicyclo[3.2.1]octane-based amino acids as reverse turn inducers have been introduced into cyclic peptidomimetics containing the RGD or DGR retro-sequence, in order to achieve a stereochemical scanning of the binding capability of the resulting molecules towards alpha(v)beta(3) and alpha(v)beta(5) integrins, resulting in retro-inverso DGR peptides as micromolar ligands. A comparative analysis between the conformational preferences of 4 and of its isomer 3, having the opposite RGD sequence, was reported with respect to the binding activity, giving insight into the factors affecting the preferential binding of 4 to the alpha(v)beta(5) integrin.

Determinants of final infarct size and incidence of aborted infarction in patients treated with primary coronary intervention and adjunctive abciximab therapy.

AIMS: Assess the determinants of final infarct size in patients successfully treated with primary percutaneous coronary intervention (PCI) and abciximab therapy and check whether infarct abortion may occur. PATIENTS, METHODS: In 208 patients we examined the parameters that predict final infarct size and the incidence of aborted infarction, defined by completely normal perfusion and regional wall motion plus >50% left ventricular ejection fraction (LVEF) in gated single-photon emission computed tomography (SPECT) acquired at one month. RESULTS: In linear regression analysis, sex (p<0.0001), high cholesterol (p<0.05), Killip class (p<0.0001), symptom-to-reperfusion time (p<0.001), admission ST segment elevation (p<0.0001), infarct related artery (p<0.05), and pre-procedural TIMI flow (p<0.002) were significant univariate predictors of final infarct size. In multiple linear regression analysis, symptom-to-reperfusion time (p<0.001), Killip class (p<0.0001), ST segment elevation (p<0.003), and sex (p<0.03) remained significant predictors, model R(2)=0.53. Aborted infarction was registered in 32 patients, more frequently female (59% versus 21%, p<0.00001), older (p<0.02), with larger prevalence of TIMI grade 3 (p<0.05) and lower ST segment elevation at admission (p<0.05). CONCLUSIONS: Sex, reperfusion delay, and initial infarct severity as indicated by Killip class and/or ST segment elevation appear the determinants of final infarct size in patients treated with primary PCI. The presence of aborted infarction seems related to the same factors and to preserved TIMI 3 flow.

Metabolic correlates of executive dysfunction. Different patterns in mild and very mild Alzheimer's disease.

This study was designed to examine the correlations between resting-state brain glucose metabolism (CMRglc), as measured with Positron Emission Tomography and performance on executive function tasks in Alzheimer's disease (AD), while taking into account the severity of cognitive deterioration. We addressed this issue in 50 AD patients, classified as very mild (n = 22) and mild (n = 28) AD on the basis of an extensive neuropsychological battery. Thirteen healthy subjects were selected as controls for the neuropsychological measures. Statistical Parametric Mapping (SPM) was used to examine voxel-wise correlations between CMRglc and scores on selected cognitive tests of executive functions: the Stroop Test, the Trail Making Test, the Dual Task and the Phonemic Fluency, while correcting for age and global CMRglc. All analyses were done separately for the two AD subgroups. The very mild AD patients showed significant associations between Stroop and Trail Making Test scores and prefrontal regions metabolism, whereas the mild AD patients exhibited more widely distributed cognitive-metabolic correlations extending to the posterior brain regions. These data suggest that a large cortical network is implicated in executive dysfunction in AD, and that the pattern of cognitive-metabolic correlations varies according to disease severity.

Prognostic implications of Tc-99m sestamibi viability imaging and subsequent therapeutic strategy in patients with chronic coronary artery disease and left ventricular dysfunction.

OBJECTIVES: The aim of the study was to verify the prognostic implications of viability detection using baseline-nitrate sestamibi imaging in patients with left ventricular (LV) dysfunction due to chronic coronary artery disease (CAD) submitted to different therapeutic strategies. BACKGROUND: The prognostic meaning of preserved viability in these patients is still debated. Sestamibi is increasingly used for myocardial perfusion scintigraphy and is being accepted also as viability tracer, but no data are available about the relationship between viability in sestamibi imaging, subsequent treatment, and patient's outcome. METHODS: Follow-up data were collected in 105 CAD patients with LV dysfunction who had undergone baseline-nitrate sestamibi perfusion imaging for viability assessment and had been later treated medically (group 1), or submitted to revascularization, which was either complete (group 2A) or incomplete (group 2B). RESULTS: Eighteen hard events (cardiac death or nonfatal myocardial infarction) were registered during the follow-up. A significantly worse event-free survival curve was observed in the patients of group 1 (p < 0.0002) and group 2B (p < 0.03) compared to those of group 2A. Using a Cox proportional hazard model, the most powerful prognostic predictors of events were the number of nonrevascularized asynergic segments with viability in sestamibi imaging (p < 0.003, risk ratio [RR] = 1.4), and the severity of CAD (p < 0.02, RR = 1.28). CONCLUSIONS: Viability detection in sestamibi imaging has important prognostic implications in CAD patients with LV dysfunction. Patients with preserved viability kept on medical therapy or submitted to incomplete revascularization represent high-risk groups.

FDG-PET in the management of germ cell tumor.

Germ cell tumor is the most common malignancy in young men. The cure rate of these patients has tremendously increased in the cisplatin era, and recent results have indicated that the management of patients with GCT is still improving. The use of FDG-PET in the management of patients with GCT has been recently investigated. This report attempts to comprehensively review new advances and delineate the potential applications of FDG-PET in GCT.

Nutrient patterns and brain biomarkers of Alzheimer's disease in cognitively normal individuals.

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-ß, Aß) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. MEASUREMENTS: Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. RESULTS: None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter. CONCLUSION: Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aß and associated neuronal impairment.

Brain perfusion abnormalities in drug-naive, lactate-sensitive panic patients: a SPECT study.

Using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime (HM-PAO), we assessed brain perfusion in seven patients with panic disorder (PD) and in five age-matched normal subjects at rest. No patient had ever received drug treatment for panic. All patients were sensitive to lactate-induced panic. Computed tomography (CT) scans did not reveal any morphological abnormalities of the brain in any of the PD patients. Two indices of cerebral perfusion were calculated; these demonstrated alterations of brain perfusion in the PD group. Significant right-left asymmetry was found in the inferior frontal cortex of the PD patients. We also observed a significant blood flow increase in the left occipital cortex and a significant decrease in the hippocampal regions bilaterally. Although the changes seen in the inferior frontal cortex and occipital cortex may be related to anxiety experienced by the patients during the study, the pattern of hippocampal hypoperfusion appears to be characteristic of panic disorder. This suggests that the hippocampal structures may play an important role in the pathophysiology of panic disorder.

Quantitation of brain perfusion with 99mTc-bicisate and single SPECT scan: comparison with microsphere measurements.

This study describes and validates in a preliminary manner a method to measure the steady-state influx constant (Ki) of 99mTc-bicisate with one single photon emission computed tomography (SPECT) scan. The method is based on the analysis of the arterial concentration of the radioactivity. The results of this quantitation procedure were compared with regional CBF (rCBF) measurements made using 99mTc-microspheres (MI). Two quantitative indexes of perfusion, fractional brain uptake (FBU) and normalized (with cerebellum) brain uptake (NBU), were also evaluated. Two SPECT studies were performed on seven cardiovascular patients who had no signs of neurological disease. In the first of these, 99mTc-bicisate was used, while in the other, which was performed 2 days later, MI were injected into the left heart ventricle. The values of the FBU, NBU, and Ki of 99mTc-bicisate were calculated in several gray and white matter brain regions of interest (ROIs) and compared with the rCBF values measured with MI in coupled ROIs. Mean FBU values were 0.00008 +/- 0.00002 and 0.00004 +/- 0.00001 in the gray and the white matter, respectively. Mean NBU values were 0.99 +/- 0.04 and 0.54 +/- 0.05, mean Ki values were 0.36 +/- 0.06 and 0.19 +/- 0.03 ml g-1 min-1 and mean rCBF values were 0.51 +/- 0.04 and 0.27 +/- 0.04 ml g-1 min-1 in gray and white matter, respectively. Analysis of variance of the regression gave different F values for the regressions with rCBF of FBU (F = 19, n = 126), NBU (F = 289, n = 112), and Ki (F = 117, n = 126).(ABSTRACT TRUNCATED AT 250 WORDS)

Characterizing an ectopic secreting carcinoid with indium-111-DTPA-D-Phe-pentetreotide.

UNLABELLED: This report describes a technique that increases the specificity of 111In-pentetreotide as evaluated in a patient with ectopic Cushing syndrome. METHODS: Two separate SPECT studies were performed with different pharmacologic protocols, both including treatment with cold octreotide. The imaging protocol provides acquisitions at 4 and 24 hr after injection. The quantitative approach was based on the ROI activity (manually designed) of an area of pathological lung uptake (ROI-T) versus background (ROI-NT). Histological, histochemical and specific mRNA measurements confirmed the presence of an SSR2 receptor carcinoid in the lung. RESULTS: The time course of ROI-T/ROI-NT is a linear increase between 4 and 24 hr. Washout with cold octreotide diminished the ROI-T activity content and the saturation protocol increased ROI-T/ROI-NT, confirming the specific nature of the uptake. CONCLUSION: Displacement and saturation protocols in 111In-pentetreotide imaging demonstrated the specificity of tumor binding.

Rest-redistribution thallium-201 SPECT to detect myocardial viability.

UNLABELLED: Rest-redistribution 201Tl imaging is currently being used for myocardial viability detection, but the ideal parameters for territory classification have not yet been defined. The aim of this study was to define the optimal criteria for detecting viable myocardium and predicting postrevascularization recovery with rest-redistribution 201Tl SPECT. METHODS: In 29 patients with left ventricular dysfunction, tracer activity within asynergic segments was quantified on rest and redistribution 201Tl SPECT. Viability was defined by the presence of functional recovery, which was detected by comparing wall motion in baseline and follow-up echocardiography. Discriminant function analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the relationship between 201Tl data and viability. RESULTS: Of 214 dysfunctioning segments (135 a-/dyskinetic), viability was demonstrated in 115 (75 a-/dyskinetic). Both rest and redistribution 201Tl activity in these segments were significantly higher than they were in the nonviable segments (p < 0.0001). Significant (> 10%) reversibility was observed in 39% of the viable and in 36% of the nonviable segments (p = 0.81). Discriminant analysis identified redistribution activity, followed by rest activity, as the most effective predictors of functional recovery. Similar areas were found under the ROC curve for rest (0.68 +/- 0.037) and for redistribution activity (0.70 +/- 0.036) (p = 0.13). ROC curve analysis identified the optimal cutoff for redistribution activity at < 60%, with 147 of 214 (69%) segments correctly classified (sensitivity = 78% and specificity = 58%). In the subset of a-/dyskinetic segments, redistribution activity presented a significantly larger ROC curve area (0.81 +/- 0.038 compared to 0.77 +/- 0.042, p < 0.05), and 103 of 135 (76%) segments were correctly classified (sensitivity = 81% and specificity = 70%). CONCLUSION: Redistribution activity is the most important parameter to be considered in rest-redistribution 201Tl to differentiate viable from nonviable segments; rest activity is also valuable, whereas the meaning of reversibility appears limited. Cutoff values about 60% appear to give the most reasonable balance between sensitivity and specificity.

An analysis of the arterial input curve for technetium-99m-HMPAO: quantification of rCBF using single-photon emission computed tomography.

Arterial radioactivity content after the intravenous administration of HMPAO in seven human subjects was analyzed. Arterial sampling of 99mTc-HMPAO was performed on each subject over a 25-min period postinjection. The lipophilic fraction of the tracer present in the blood was rapidly extracted with octanol. An analysis of the time course of the extracted and nonextracted octanol fractions was performed in order to calculate the arterial input of the tracer available for brain extraction. HMPAO net regional brain clearances were then calculated and compared with rCBF values obtained in the same patients using 99mTc-microspheres injected into the left ventricle of the heart. HMPAO brain clearances were 0.41 +/- 0.01 and 0.27 +/- 0.01 ml/min/g for grey and white matter, respectively. Linear regression analysis was performed and the following result was obtained: clearance (HMPAO) = 0.07 + 0.43 . rCBF with a high significance (p less than 0.001). This equation can be used for the transformation of HMPAO clearances into rCBF values. Our study demonstrates that by using HMPAO and SPECT it is possible to obtain a quantitative estimate of rCBF in humans.

Left ventricular cavity-to-myocardium count ratio in technetium-99m-sestamibi SPECT in the detection of resting left ventricular dysfunction.

UNLABELLED: The aim of this study was to assess the value of the cavity-to-myocardium count ratio (C/M ratio) calculated in resting 99mTc-sestamibi SPECT images to identify patients with depressed left ventricular ejection fraction (LVEF). METHODS: In the 95 patients studied, the C/M ratio was calculated from the midventricular short-axis slice using regions of interest drawn in the center of the cavity and in the most active area of the ventricular wall; its value was compared with LVEF measured using two-dimensional echocardiography. RESULTS: The C/M ratio correlated with LVEF (r = 0.6, p < 0.000001) and was significantly lower in patients with abnormal LVEF than those with normal LVEF: 0.026 +/- 0.028 versus 0.125 +/- 0.093, p < 0.000001. In the entire patient population, a C/M ratio < 0.07 identified the patients with depressed LVEF with a 94% sensitivity, 71% specificity and 82% accuracy. CONCLUSION: The resting 99mTc-sestamibi C/M ratio is a useful parameter in identifying patients with depressed LVEF directly from the SPECT perfusion images.

First-pass cerebral extraction of benzamide-derivative radiotracers for SPECT.

Central dopaminergic receptors are widely studied for their importance in the pathophysiology of neurological and psychiatric diseases. We have investigated the cerebral delivery kinetics of three dopaminergic ligands in rats through the use of an indicator fractionation method to measure the tracer's regional influx rate constant with respect to regional blood flow. The aim is to collect the in vivo kinetic parameters of the radioligand cerebral distribution, which are necessary if, dealing with SPECT and "trapped" tracers, one wishes to analyse data using a graphical approach.

Compensation of spatial system response in SPECT with conjugate gradient reconstruction technique.

A procedure for the determination of the system matrix in single photon emission tomography (SPECT) is described which uses the conjugate gradient reconstruction technique in order to take into account the variable system resolution of a camera equipped with parallel-hole collimators. The procedure involves the acquisition of the system line spread functions (LSF) in the region occupied by the object to be studied. Those data are used to generate a set of weighting factors based on the assumption that the LSFs of the collimated camera are of Gaussian shape with the full width at half maximum (FWHM) linearly dependent on the source depth in the span of image space. The factors are stored on a disc file for subsequent use in the reconstruction process. Afterwards the reconstruction is performed using the conjugate gradient method with the system matrix modified by the incorporation of these precalculated factors in order to take into account the variable geometrical system response. The set of weighting factors is regenerated whenever the acquisition conditions are changed (collimator, radius of rotation). In the case of an ultra high resolution (UHR) collimator 2000 weighting factors need to be calculated. The modification of the system matrix for the geometrical response allows the number of iterations to increase, considerably improving image definition without the appearance of noise artifacts. Moreover, phantom studies show that the number of iterations is less critical because of improved stability in the convergence to the solution. For brain studies of patients 10-15 iterations are usually performed. Studies with a single line source give a value between 7 and 8 mm for the FWHM of the point spread function (PSF) when the conjugate gradient method with modified system matrix is used on data acquired with a UHR collimator, whereas without the modification of the system matrix the result is 9 mm FWHM, if filtered backprojection (FBP) is used with the same filter as in the clinical studies the result is 15 mm FWHM. The results of this work show that proper definition of the system matrix using conjugate gradients influences the quality of the reconstruction remarkably. Nevertheless, further work has to be done in order to assess to what extent the system matrix is ill-conditioned and, eventually, to define a suitable regularization technique.

Fertility and semen quality of workers exposed to high temperatures in the ceramics industry.

The objective of this study was to test the hypothesis that chronic occupational exposure to high temperatures may be detrimental to male reproduction. The study was based on 92 healthy ceramics oven operators with a long exposure to high temperatures, and 87 controls, recruited from the shipment department of the same industry. Interviews with all subjects provided data on sociodemographic characteristics, health status, and fertility problems. Semen analysis was carried out on 46 of the workers exposed to high temperatures, and 14 of the controls, and included evaluation of the sperm concentration, morphology, and motility, including computer-assisted sperm motion analysis (velocity, linearity, ALH, BCF). The results of the questionnaire showed that exposed individuals had a higher incidence of childlessness and of self-reported difficulty in conceiving than controls. The semen analysis showed no significant differences except in sperm velocity. Although differences in semen parameters, taken singly, were not statistically significant, the overall evaluation of the sperm parameters indicated a higher prevalence of pathologic sperm profiles among the exposed compared to the controls.

The role of whole body scan and skeletal radiography in the preoperative staging of breast cancer.

442 patients with breast cancer were studied by means of radiologic and scintigraphic examination of the skeleton to detect the presence of bone metastases. All the patients have been clinically followed-up for a mean period of 22 months. The overall prevalence of bone metastases at staging was 4.5%. Bone scan showed a higher sensitivity in detecting bone metastases (90% vs 45%) and a lower positive predictive value (60% vs 75%) with respect to X-ray examination. In the presence series no asymptomatic case with bone metastases was found in limited stages (T1-T2 N0-N1). The authors suggest that the bone scan be routinely included in the staging of advanced breast cancer cases and that the use of this procedure be restricted to the symptomatic patients in the more limited stages.

Staging breast cancer--screening for occult metastases.

The authors report on 1,017 consecutive breast cancer cases without symptomatic metastases staged by means of chest X-ray (CXR), skeletal survey (BXR) and bone scintigraphy (BS). Occult metastases (DM) detection rate was 0.88%: 0.29% for lung and 0.59% for bone DM. The detection rate was correlated with clinical stage: 0.36% for stage I, 0.20% for stage II, 0.26% for stages I and II, and 2.77% for stage III cases. The sensitivity based on DM cases prevalent or surfacing within 6 months of follow-up was 0.30 for CXR, 0.22 for BXR and 0.55 for BS; specificity was 0.99, 0.98 and 0.90, respectively. The study confirms the possibility of early detection of DM with preoperative staging, but the extremely low detection rates in stage I and II cancers do not advise such a routine procedure. The higher detection rate of DM may suggest adoption of the routine staging procedure in stage III cancers. In these cases, although no evidence is available of a favorable prognostic impact of early detection and treatment of DM, an unnecessary mastectomy could be avoided in about 3% of cases in the presence of DM detected by the staging procedure.

Usefulness of the TRH test in the management of patients with differentiated thyroid cancer.

Thirty patients thyroidectomized for differentiated thyroid cancer were studied. Serum TSH was assayed in basal conditions and after TRH stimulation, while patients were in suppressive therapy with thyroid hormones. The basal TSH was normal in all the patients and less than 2 microU/ml in 20 patients. The TRH test was negative (no TSH response) in 27 patients and in all the cases with the basal TSH lower than 2 microU/ml.

World Wide Web interface for advanced SPECT reconstruction algorithms implemented on a remote massively parallel computer.

Data from Single Photon Emission Computed Tomography (SPECT) studies are blurred by inevitable physical phenomena occurring during data acquisition. These errors may be compensated by means of reconstruction algorithms which take into account accurate physical models of the data acquisition procedure. Unfortunately, this approach involves high memory requirements as well as a high computational burden which cannot be afforded by the computer systems of SPECT acquisition devices. In this work the possibility of accessing High Performance Computing and Networking (HPCN) resources through a World Wide Web interface for the advanced reconstruction of SPECT data in a clinical environment was investigated. An iterative algorithm with an accurate model of the variable system response was ported on the Multiple Instruction Multiple Data (MIMD) parallel architecture of a Cray T3D massively parallel computer. The system was accessible even from low cost PC-based workstations through standard TCP/IP networking. A speedup factor of 148 was predicted by the benchmarks run on the Cray T3D. A complete brain study of 30 (64 x 64) slices was reconstructed from a set of 90 (64 x 64) projections with ten iterations of the conjugate gradients algorithm in 9 s which corresponds to an actual speed-up factor of 135. The technique was extended to a more accurate 3D modeling of the system response for a true 3D reconstruction of SPECT data; the reconstruction time of the same data set with this more accurate model was 5 min. This work demonstrates the possibility of exploiting remote HPCN resources from hospital sites by means of low cost workstations using standard communication protocols and an user-friendly WWW interface without particular problems for routine use.

[Sequential scintiscanning with 99mTc-HIDA in the study of some aspects of post-operative dynamics of the proximal digestive tract]. / La scintigrafia sequenziale con 99mTc-HIDA nello studio di alcuni aspetti della dinamica post-operatoria del digerente prossimale.

The authors exploited the elective biliary excretion of 99mTc-HIDA at adequate concentrations to afford visibility of intestinal segments more directly wetted by bile in a study of sequential hepatobiliary scintigraphy designed to explore the parts of the duodenum and jejunum that are excluded to the transit of gastrointestinal contents in many surgical procedures involving the proximal digestive tract. They illustrate their case material with several representative examples; these are described in detail to show the validity, usefulness and versatility of the scintigraphic technic under discussion.